7, 12-Dimethylbenz[a]anthracene-deoxyribonucleoside adduct formation in vivo: evidence for the formation and binding of a monohydroxymethyl-DMBA metabolite to rat liver DNA

The polycyclic aromatic hydrocarbon, 7, 12-dimethyl benz[a]anthracene(DMBA) is a potent carcinogen to the female Sprague-Dawley rat,and when administered under conditions that have been shownto produce cancer, results in extensive formation of hydrocarbon-deoxyribonucleosideadducts. Sephadex LH-20 and reverse-phase h.p.l.c. and spectrofluorometricanalysis of these adducts demonstrate that at least one adductresults from the binding of 7, 12-dimethylbenz[a]anthracene-1,2, 3, 4-tetrahydro-3, 4-dihydroxy-1, 2-oxide. In these experiments,employing i.p. administration of the hydrocarbon, a second morepolar adduct was observed. Evidence is presented that this adductresults from the formation of a monohydroxymethyl-methylbenz[a]anthracene-A-ring-diol-epoxide.While both of the monohydroxymethyl-DMBA metabolites have beenshown to bind cellular DNA following their administration thisis the first evidence of monohydroxymethyl-DMBA-deoxyribonucleosideadducts being formed after the administration of DMBA per se.The evidence suggests that this more polar adduct is a 7-hydroxymethyl-12-methylbenz[a]anthracenedeoxyribonucleosideadduct.